CA2508657C - Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists - Google Patents

Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists Download PDF

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Publication number: CA2508657C
Authority: CA; Canada
Prior art keywords: trans; alkyl; compound; mol; amino
Prior art date: 2002-12-23
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2508657A

Other languages

English (en)

French (fr)

Other versions

CA2508657A1 (en

Inventor

Frans Eduard Janssens

Francois Maria Sommen

Benoit Christian Albert Ghislain De Boeck

Joseph Elisabeth Leenaerts

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Janssen Pharmaceutica NV

Original Assignee

Janssen Pharmaceutica NV

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-12-23

Filing date

2003-12-17

Publication date

2013-02-19

2003-12-17 Application filed by Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV

2004-07-08 Publication of CA2508657A1 publication Critical patent/CA2508657A1/en

2013-02-19 Application granted granted Critical

2013-02-19 Publication of CA2508657C publication Critical patent/CA2508657C/en

2023-12-17 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

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QUVPEYUQPVHCPV-UHFFFAOYSA-N 1-piperidin-4-yl-4-pyrrolidin-3-ylpiperazine Chemical class C1NCCC1N1CCN(C2CCNCC2)CC1 QUVPEYUQPVHCPV-UHFFFAOYSA-N 0.000 title abstract description 4
239000005557 antagonist Substances 0.000 title description 26
150000001875 compounds Chemical class 0.000 claims abstract description 277
238000002360 preparation method Methods 0.000 claims abstract description 92
206010047700 Vomiting Diseases 0.000 claims abstract description 36
150000003839 salts Chemical class 0.000 claims abstract description 34
239000002253 acid Substances 0.000 claims abstract description 27
239000003814 drug Substances 0.000 claims abstract description 21
208000019901 Anxiety disease Diseases 0.000 claims abstract description 19
230000036506 anxiety Effects 0.000 claims abstract description 12
201000000980 schizophrenia Diseases 0.000 claims abstract description 10
125000000815 N-oxide group Chemical group 0.000 claims abstract 2
-1 cyano, hydroxy, formyl Chemical group 0.000 claims description 88
125000000217 alkyl group Chemical group 0.000 claims description 42
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
125000004432 carbon atom Chemical group C* 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
208000002551 irritable bowel syndrome Diseases 0.000 claims description 21
125000003545 alkoxy group Chemical group 0.000 claims description 18
229930195734 saturated hydrocarbon Natural products 0.000 claims description 18
238000000034 method Methods 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
125000004122 cyclic group Chemical group 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
208000002193 Pain Diseases 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
230000036407 pain Effects 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
125000004043 oxo group Chemical group O=* 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
230000000694 effects Effects 0.000 claims description 8
125000001041 indolyl group Chemical group 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 8
125000001544 thienyl group Chemical group 0.000 claims description 8
208000021891 Micturition disease Diseases 0.000 claims description 7
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239000004480 active ingredient Substances 0.000 claims description 7
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
208000006673 asthma Diseases 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
125000000168 pyrrolyl group Chemical group 0.000 claims description 7
230000020341 sensory perception of pain Effects 0.000 claims description 7
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
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230000027288 circadian rhythm Effects 0.000 claims description 6
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125000003386 piperidinyl group Chemical group 0.000 claims description 6
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125000003226 pyrazolyl group Chemical group 0.000 claims description 6
125000002098 pyridazinyl group Chemical group 0.000 claims description 6
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125000004429 atom Chemical group 0.000 claims description 5
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125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
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125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000160 oxazolidinyl group Chemical group 0.000 claims description 4
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125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
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BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
125000005883 dithianyl group Chemical group 0.000 claims description 2
125000002636 imidazolinyl group Chemical group 0.000 claims description 2
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
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125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
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125000004306 triazinyl group Chemical group 0.000 claims description 2
125000001425 triazolyl group Chemical group 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 12
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims 2
HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 claims 1
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VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 32
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235000019341 magnesium sulphate Nutrition 0.000 description 30
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CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 26
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
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QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 19
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Classifications

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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
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- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
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- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
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- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Pulmonology (AREA)
Immunology (AREA)
Otolaryngology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA2508657A 2002-12-23 2003-12-17 Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists Expired - Fee Related CA2508657C (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EPPCT/EP02/14831		2002-12-23
EP0214831		2002-12-23
PCT/EP2003/051041 WO2004056799A2 (en)	2002-12-23	2003-12-17	Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists

Publications (2)

Publication Number	Publication Date
CA2508657A1 CA2508657A1 (en)	2004-07-08
CA2508657C true CA2508657C (en)	2013-02-19

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ID=32668698

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CA2508657A Expired - Fee Related CA2508657C (en)	2002-12-23	2003-12-17	Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists

Country Status (30)

Country	Link
US (1)	US7795261B2 (ar)
EP (1)	EP1581518B1 (ar)
JP (1)	JP4746878B2 (ar)
KR (1)	KR101049073B1 (ar)
CN (1)	CN100586945C (ar)
AR (1)	AR042651A1 (ar)
AT (1)	ATE500242T1 (ar)
AU (1)	AU2003302488B2 (ar)
BR (1)	BR0317658A (ar)
CA (1)	CA2508657C (ar)
CL (1)	CL2003002725A1 (ar)
CY (1)	CY1112601T1 (ar)
DE (1)	DE60336266D1 (ar)
DK (1)	DK1581518T3 (ar)
EA (1)	EA009078B1 (ar)
ES (1)	ES2361161T3 (ar)
HR (1)	HRP20050556B1 (ar)
IL (1)	IL169336A (ar)
JO (1)	JO2696B1 (ar)
MX (1)	MXPA05006887A (ar)
MY (1)	MY145135A (ar)
NO (1)	NO331174B1 (ar)
NZ (1)	NZ541035A (ar)
PA (1)	PA8593301A1 (ar)
PL (1)	PL376048A1 (ar)
PT (1)	PT1581518E (ar)
SI (1)	SI1581518T1 (ar)
TW (1)	TWI329109B (ar)
UA (1)	UA80584C2 (ar)
WO (1)	WO2004056799A2 (ar)

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FR2847160A1 (fr) *	2002-11-20	2004-05-21	Oreal	Composition capillaire contenant un compose pyrasol-carboxamide, son utilisation pour stimuler la pousse des cheveux et/ou freiner leur chute
EA015517B1 (ru)	2004-04-13	2011-08-30	Инсайт Корпорейшн	Производные пиперазинилпиперидина в качестве антагонистов хемокинового рецептора
WO2005123081A2 (en) *	2004-06-22	2005-12-29	Janssen Pharmaceutica N.V.	(2-benzyl-4-{4-[1-(tetrahydrofuran-3-carbonyl)-pyrrolidin-3-yl]-piperazin-1-yl}-piperidin-1-yl)-(3,5-trifluoromethyl-phenyl))-methanone for the treatment of schizophrenia
WO2006071875A1 (en)	2004-12-29	2006-07-06	Millennium Pharmaceuticals, Inc.	Compounds useful as chemokine receptor antagonists
WO2006071958A1 (en)	2004-12-29	2006-07-06	Millennium Pharmaceuticals, Inc.	Compounds useful as chemokine receptor antagonists
NZ556628A (en) *	2005-03-08	2009-09-25	Janssen Pharmaceutica Nv	Diaza-spiro-[4.4]-nonane derivatives as neurokinin (NK1) antagonists
DE102005038947A1 (de) *	2005-05-18	2006-11-30	Grünenthal GmbH	Substituierte Benzo[d]isoxazol-3-yl-amin-Verbindungen und deren Verwendung in Arzneimitteln
CN101534824A (zh) *	2006-11-17	2009-09-16	艾博特公司	作为化学活素受体拮抗剂的氨基吡咯烷
RU2442786C2 (ru) *	2007-03-31	2012-02-20	Интервет Интернэшнл Б.В.	Способы получения зилпатерола и его солей
CA2800324C (en) *	2007-03-31	2016-02-16	Intervet International B.V.	Zilpaterol and salts thereof for use in increasing the rate of weight gain, improved feed efficiency and/or increasing carcass leanness in a bovine
MX2009010499A (es)	2007-03-31	2009-10-19	Intervet Int Bv	Procesos para elaborar zilpaterol y sales del mismo.
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
MX354786B (es)	2007-06-04	2018-03-21	Synergy Pharmaceuticals Inc	Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos.
CA2689560A1 (en)	2007-06-07	2008-12-11	F.Hoffmann-La Roche Ag	Prolinamide derivatives as nk3 antagonists
AU2009270833B2 (en)	2008-07-16	2015-02-19	Bausch Health Ireland Limited	Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
US8507535B2 (en) *	2010-07-07	2013-08-13	Hoffmann-La Roche Inc.	Methyl-pyrrolidine ether derivatives
EA201590197A1 (ru) *	2012-08-23	2015-07-30	Алиос Биофарма, Инк.	Соединения для лечения парамиксовирусных вирусных инфекций
AU2014235215A1 (en)	2013-03-15	2015-10-01	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
AU2014235209B2 (en)	2013-03-15	2018-06-14	Bausch Health Ireland Limited	Guanylate cyclase receptor agonists combined with other drugs
SMT201900719T1 (it)	2015-05-18	2020-01-14	Nerre Therapeutics Ltd	Antagonista del recettore nk-1/nk-3 per il trattamento delle vampate di calore
AU2019233606B2 (en)	2018-03-14	2024-10-03	KaNDy Therapeutics Limited	Novel pharmaceutical formulation comprising dual NK-1/NK-3 receptor antagonists
CA3121202A1 (en)	2018-11-30	2020-06-04	Nuvation Bio Inc.	Pyrrole and pyrazole compounds and methods of use thereof
US12533358B1 (en)	2025-05-14	2026-01-27	Bayer Consumer Care Ag	Methods of treatment with elinzanetant

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US5589489A (en) *	1993-12-15	1996-12-31	Zeneca Limited	Cyclic amide derivatives for treating asthma
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MY141736A (en)	2002-10-08	2010-06-15	Elanco Animal Health Ireland	Substituted 1,4-di-piperidin-4-yi-piperazine derivatives and their use as neurokinin antagonists

2003
- 2003-12-15 JO JO2003174A patent/JO2696B1/ar active
- 2003-12-17 UA UAA200505412A patent/UA80584C2/uk unknown
- 2003-12-17 US US10/540,447 patent/US7795261B2/en not_active Expired - Fee Related
- 2003-12-17 WO PCT/EP2003/051041 patent/WO2004056799A2/en not_active Ceased
- 2003-12-17 DE DE60336266T patent/DE60336266D1/de not_active Expired - Lifetime
- 2003-12-17 SI SI200331992T patent/SI1581518T1/sl unknown
- 2003-12-17 JP JP2004561504A patent/JP4746878B2/ja not_active Expired - Fee Related
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- 2003-12-17 ES ES03810849T patent/ES2361161T3/es not_active Expired - Lifetime
- 2003-12-17 PT PT03810849T patent/PT1581518E/pt unknown
- 2003-12-17 NZ NZ541035A patent/NZ541035A/en not_active IP Right Cessation
- 2003-12-17 AT AT03810849T patent/ATE500242T1/de active
- 2003-12-17 CN CN200380106356A patent/CN100586945C/zh not_active Expired - Fee Related
- 2003-12-17 MX MXPA05006887A patent/MXPA05006887A/es active IP Right Grant
- 2003-12-17 EA EA200501041A patent/EA009078B1/ru not_active IP Right Cessation
- 2003-12-17 DK DK03810849.4T patent/DK1581518T3/da active
- 2003-12-17 PL PL03376048A patent/PL376048A1/xx not_active Application Discontinuation
- 2003-12-17 HR HRP20050556AA patent/HRP20050556B1/hr not_active IP Right Cessation
- 2003-12-17 BR BR0317658-4A patent/BR0317658A/pt not_active IP Right Cessation
- 2003-12-17 AU AU2003302488A patent/AU2003302488B2/en not_active Ceased
- 2003-12-17 CA CA2508657A patent/CA2508657C/en not_active Expired - Fee Related
- 2003-12-17 KR KR1020057009197A patent/KR101049073B1/ko not_active Expired - Fee Related
- 2003-12-19 PA PA20038593301A patent/PA8593301A1/es unknown
- 2003-12-19 MY MYPI20034909A patent/MY145135A/en unknown
- 2003-12-22 CL CL200302725A patent/CL2003002725A1/es unknown
- 2003-12-22 TW TW092136343A patent/TWI329109B/zh not_active IP Right Cessation
- 2003-12-22 AR ARP030104776A patent/AR042651A1/es unknown
2005
- 2005-06-22 IL IL169336A patent/IL169336A/en not_active IP Right Cessation
- 2005-07-21 NO NO20053569A patent/NO331174B1/no not_active IP Right Cessation
2011
- 2011-06-01 CY CY20111100532T patent/CY1112601T1/el unknown

Also Published As

Publication number	Publication date
US7795261B2 (en)	2010-09-14
WO2004056799A2 (en)	2004-07-08
IL169336A (en)	2013-01-31
DE60336266D1 (de)	2011-04-14
KR20050085098A (ko)	2005-08-29
BR0317658A (pt)	2005-12-06
PL376048A1 (en)	2005-12-12
SI1581518T1 (sl)	2011-06-30
EP1581518B1 (en)	2011-03-02
CN1726207A (zh)	2006-01-25
ATE500242T1 (de)	2011-03-15
KR101049073B1 (ko)	2011-07-15
WO2004056799A3 (en)	2004-08-12
MXPA05006887A (es)	2005-08-16
TWI329109B (en)	2010-08-21
JP4746878B2 (ja)	2011-08-10
ES2361161T3 (es)	2011-06-14
CA2508657A1 (en)	2004-07-08
IL169336A0 (en)	2007-07-04
HK1087703A1 (zh)	2006-10-20
US20060040950A1 (en)	2006-02-23
PA8593301A1 (es)	2004-08-31
EP1581518A2 (en)	2005-10-05
CN100586945C (zh)	2010-02-03
EA200501041A1 (ru)	2005-12-29
PT1581518E (pt)	2011-05-12
NZ541035A (en)	2008-05-30
AU2003302488A1 (en)	2004-07-14
JO2696B1 (ar)	2013-03-03
CY1112601T1 (el)	2016-02-10
JP2006514027A (ja)	2006-04-27
UA80584C2 (uk)	2007-10-10
HRP20050556A2 (en)	2006-07-31
DK1581518T3 (da)	2011-06-06
EA009078B1 (ru)	2007-10-26
NO20053569L (no)	2005-09-15
AR042651A1 (es)	2005-06-29
TW200500359A (en)	2005-01-01
NO20053569D0 (no)	2005-07-21
MY145135A (en)	2011-12-30
AU2003302488B2 (en)	2009-10-08
HRP20050556B1 (hr)	2014-03-28
NO331174B1 (no)	2011-10-24
CL2003002725A1 (es)	2005-04-08

Legal Events

Date	Code	Title	Description
2008-10-29	EEER	Examination request
2017-01-30	MKLA	Lapsed	Effective date: 20161219

Publication	Publication Date	Title
CA2508657C (en)	2013-02-19	Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists
AU2003299249B2 (en)	2010-05-27	Substituted 1-piperidin-4-yl-4-azetidin-3-yl-piperazine derivatives and their use as neurokinin antagonists
EP1551804B1 (en)	2008-12-24	Substituted 1,4-di-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists
EP1735313B1 (en)	2010-06-23	Substituted diaza-spiro-[4.5]-decane derivatives and their use as neurokinin antagonists
EP1735312B1 (en)	2008-12-10	Substituted diaza-spiro-[5.5 -undecane derivatives and their use as neurokinin antagonists
EP1737838B1 (en)	2008-05-21	Substituted 4-alkyl- and 4-alkanoyl-piperidine derivatives and their use as neurokinin antagonists
EP1874783B1 (en)	2010-05-26	Substituted oxa-diaza-spiro-[5.5]-undecanone derivatives and their use as neurokinin antagonists
CA2509090C (en)	2012-01-24	Substituted 4-(4-piperidin-4-yl-piperazin-1-yl)-azepane derivatives and their use as neurokinin antagonists
CA2509088C (en)	2012-01-24	Substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists
WO2004056772A1 (en)	2004-07-08	Substituted 1,4-di-piperidin-4-yl-piperazine derivatives and their use as tachykinin antagonists
EP1578425B1 (en)	2007-11-21	Substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists